Cosynthesis of cargo-loaded hydroxyapatite/alginate core-shell nanoparticles (HAP@Alg) as pH-responsive nanovehicles by a pre-gel method

Yung He Liang, Chia Hung Liu, Shih Hsiang Liao, Yuan Yun Lin, Hao Wei Tang, Shin Yun Liu, I. Rue Lai, Kevin C W Wu

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

A new core-shell nanostructure consisting of inorganic hydroxyapatite (HAP) nanoparticles as the core and organic alginate as the shell (denoted as HAP@Alg) was successfully synthesized by a pre-gel method and applied to pH-responsive drug delivery systems (DDS). HAP@Alg nanoparticles have the advantages of hydroxyapatite and alginate, where hydroxyapatite provides pH-responsive degradability, and alginate provides excellent biocompatibility and COOH functionality. Through the subsequent addition of CaCl2 and phosphate solutions to the alginate solution, HAP@Alg nanoparticles with controllable particle sizes (ranging from 160 to 650 nm) were obtained, and their core-shell structure was confirmed through transmission electron microscopy (TEM) observation. Rhodamine 6G (R6G), a positively charged dye, was selected as a model drug for pH-sensitive DDS. R6G was encapsulated in the HAP/Alg nanoparticles upon synthesis, and its loading efficiency could reach up to approximately 63.0%. The in vitro release behavior of the loaded R6G at different pH values was systematically studied, and the results indicated that more R6G molecules were released at lower pH conditions. For example, after releasing for 8 h, the release amount of R6G at pH 2.0 was 2.53-fold the amount at pH 7.4. We attributed this pH-sensitive release behavior to the dissolution of the HAP core in acidic conditions. The results of the MTT assay and confocal laser scanning microscopy indicated that the HAP@Alg were successfully uptaken by liver cancer cells (HepG2) without apparent cytotoxicity. The synthesized HAP@Alg nanoparticles show great potential as drug nanovehicles with high biocompatibility, enhanced drug loading, and pH-responsive features for future intracellular DDS.

Original languageEnglish
Pages (from-to)6720-6727
Number of pages8
JournalACS Applied Materials and Interfaces
Volume4
Issue number12
DOIs
Publication statusPublished - Dec 26 2012

Fingerprint

Alginate
Durapatite
Hydroxyapatite
Gels
Nanoparticles
Biocompatibility
alginic acid
Pharmaceutical Preparations
Cytotoxicity
Liver
Assays
Nanostructures
Microscopic examination
Dissolution
Phosphates
Coloring Agents
Dyes
Particle size
Cells
rhodamine 6G

Keywords

  • alginate, nanoparticles
  • DDS
  • HepG2
  • hydroxyapatite
  • pH-responsive release

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Cosynthesis of cargo-loaded hydroxyapatite/alginate core-shell nanoparticles (HAP@Alg) as pH-responsive nanovehicles by a pre-gel method. / Liang, Yung He; Liu, Chia Hung; Liao, Shih Hsiang; Lin, Yuan Yun; Tang, Hao Wei; Liu, Shin Yun; Lai, I. Rue; Wu, Kevin C W.

In: ACS Applied Materials and Interfaces, Vol. 4, No. 12, 26.12.2012, p. 6720-6727.

Research output: Contribution to journalArticle

Liang, Yung He ; Liu, Chia Hung ; Liao, Shih Hsiang ; Lin, Yuan Yun ; Tang, Hao Wei ; Liu, Shin Yun ; Lai, I. Rue ; Wu, Kevin C W. / Cosynthesis of cargo-loaded hydroxyapatite/alginate core-shell nanoparticles (HAP@Alg) as pH-responsive nanovehicles by a pre-gel method. In: ACS Applied Materials and Interfaces. 2012 ; Vol. 4, No. 12. pp. 6720-6727.
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abstract = "A new core-shell nanostructure consisting of inorganic hydroxyapatite (HAP) nanoparticles as the core and organic alginate as the shell (denoted as HAP@Alg) was successfully synthesized by a pre-gel method and applied to pH-responsive drug delivery systems (DDS). HAP@Alg nanoparticles have the advantages of hydroxyapatite and alginate, where hydroxyapatite provides pH-responsive degradability, and alginate provides excellent biocompatibility and COOH functionality. Through the subsequent addition of CaCl2 and phosphate solutions to the alginate solution, HAP@Alg nanoparticles with controllable particle sizes (ranging from 160 to 650 nm) were obtained, and their core-shell structure was confirmed through transmission electron microscopy (TEM) observation. Rhodamine 6G (R6G), a positively charged dye, was selected as a model drug for pH-sensitive DDS. R6G was encapsulated in the HAP/Alg nanoparticles upon synthesis, and its loading efficiency could reach up to approximately 63.0{\%}. The in vitro release behavior of the loaded R6G at different pH values was systematically studied, and the results indicated that more R6G molecules were released at lower pH conditions. For example, after releasing for 8 h, the release amount of R6G at pH 2.0 was 2.53-fold the amount at pH 7.4. We attributed this pH-sensitive release behavior to the dissolution of the HAP core in acidic conditions. The results of the MTT assay and confocal laser scanning microscopy indicated that the HAP@Alg were successfully uptaken by liver cancer cells (HepG2) without apparent cytotoxicity. The synthesized HAP@Alg nanoparticles show great potential as drug nanovehicles with high biocompatibility, enhanced drug loading, and pH-responsive features for future intracellular DDS.",
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AU - Liao, Shih Hsiang

AU - Lin, Yuan Yun

AU - Tang, Hao Wei

AU - Liu, Shin Yun

AU - Lai, I. Rue

AU - Wu, Kevin C W

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